A Synthetic Oligosaccharide Resembling <i>Francisella tularensis</i> Strain 15 <i>O</i> ‐Antigen Capsular Polysaccharide as a Lead for Tularemia Diagnostics and Therapeutics

Abstract Francisella tularensis , a category A bioterrorism agent, causes tularemia in many animal species. F. tularensis subspecies tularensis (type A) and holarctica (type B) are mainly responsible for human tularemia. The high mortality rate of 30–60 % caused by F. tularensis subspecies tularensis if left untreated and the aerosol dispersal renders this pathogen a dangerous bioagent. While a live attenuated vaccine strain (LVS) of F. tularensis type B does not provide sufficient protection against all forms of tularemia infections, a significant level of protection against F. tularensis has been observed for both passive and active immunization of mice with isolated O ‐antigen capsular polysaccharide. Well‐defined, synthetic oligosaccharides offer an alternative approach towards the development of glycoconjugate vaccines. To identify diagnostics and therapeutics leads against tularemia, a collection of F. tularensis strain 15 O ‐antigen capsular polysaccharide epitopes were chemically synthesized. Glycan microarrays containing synthetic glycans were used to analyze the sera of tularemia‐infected and non‐infected animals and revealed the presence of IgG antibodies against the glycans. Two disaccharide ( 13 and 18 ), both bearing a unique formamido moiety, were identified as minimal glycan epitopes for antibody binding. These epitopes are the starting point for the development of diagnostics and therapeutics against tularemia.